Single intubation of DMBA to 50-day-old rats produces mammary carcinomas at 100-120 days of age. The tumor production was preceded by changes in the cAMP system: Within 24 hr post DMBA intubation, the intracellular cAMP level and adenylate cyclase activity increased while cAMP-dependent protein kinase activity decreased in the mammary gland. DibutyrylcAMP orally administered blocked these changes in the cAMP system and suppressed tumor production. Thus, aberration of the cAMP system is an early event in DMBA-induced carcinogenesis and exogenous DBcAMP blocks this event.